The present invention relates to methods for treating hypercholesterolemia, hyperlipidemia, and atherosclerosis in mammals by ingesting a stabilized rice bran derivative.
Hypercholesterolemia is a condition with elevated levels of circulating total cholesterol, LDL-cholesterol and VLDL-cholesterol as per the guidelines of the Expert Panel Report of the National Cholesterol Educational Program (NCEP) of Detection, Evaluation of Treatment of high cholesterol in adults (see, Arch. Int. Med. (1988) 148, 36-39). In particular, high level of LDL and VLDL are positively associated with coronary arteriosclerosis while the high levels of high density lipoproteins (HDL) are negative risk factors. The role of LDL oxidation is gaining much attention in the literature. It is well documented that LDL becomes oxidatively stressed under pathological conditions and is no longer recognized by the LDL receptors. The oxidized LDL is taken up by macrophages within the subendothelial space, leading to the formation of fatty streaks which are the basis of most advanced lesions.
Hypercholesterolemia is implicated as a high risk factor of cardiovascular disease (CVD), including arteriosclerosis, atherosclerosis and xanthomatosis in humans. Hypercholesterolemia is influenced by diet, heredity, environment, life style, diseases and stress, leading to heart attacks and strokes at an early age.
Hyperlipidemia is a condition where the blood lipid parameters are elevated. The lipids fractions in the circulating blood are, total cholesterol (TC), low density lipoproteins (LDL), very low density lipoproteins (VLDL) and triglycerides (TG). As per the American Heart Association guidelines, the safe levels are represented below. Active treatment by diet modifications and drugs are necessary to reduce the risk of fatality when the levels go abnormal.
Hyperlipidemia results from diet, heredity, lifestyle, environment, familial diseases, or stress. The condition may be inherited or may be secondary to another disorder, such as Systemic Lupus Erythematosus (SLE), Hypothyroidism, Nephrotic Syndrome, Cushing""s Syndrome, Diabetes Mellitus, obesity, alcoholism, Corticosteroid Therapy or Estrogen Therapy.
Hyperlipidemia predisposes one to coronary heart disease, cancer and obesity. Hyperlipidemia is one of the high risk factors useful in the early diagnosis of these life threatening diseases. To some extent, hyperlipidemia can be corrected by diet modifications and treatment with drugs.
Atherosclerosis is a cardiovascular condition occurring as a result of narrowing down of the arterial walls. The narrowing is due to the formation of plaques (raised patches) or streaks in the inner lining of the arteries. These plaques consist of foam cells of low-density lipoproteins, oxidized-LDL, decaying muscle cells, fibrous tissue, clumps of blood platelets, cholesterol, and sometimes calcium. They tend to form in regions of turbulent blood flow and are found most often in people with high concentrations of cholesterol in the bloodstream. The number and thickness of plaques increase with age, causing loss of the smooth lining of the blood vessels and encouraging the formation of thrombi (blood clots). Sometimes fragments of thrombi break off and form emboli, which travel through the bloodstream and block smaller vessels.
The blood supply is restricted to the heart, eventually forming a blood clot leading to death. The major causes of atherosclerosis are hypercholesterolemia and hyperlipidemia is high circulating cholesterol and high lipids like LDL-cholesterol and triglycerides in the blood. These lipids are deposited in the arterial walls, obstructing the blood flow and forming atherosclerotic plaques leading to death.
Atherosclerosis is responsible for more deaths in the U.S. than any other single condition. Atherosclerotic heart disease involving the coronary arteries is the most common single cause of death, accounting for one third of all deaths. Atherosclerotic interference with blood supply to the brain (causing stroke) is the third most common cause of death after cancer. Atherosclerosis also causes a great deal of serious illness by reducing the blood flow in other major arteries, such as those to the kidneys, the legs and the intestines.
Medication is not a satisfactory treatment because much of the damage to the artery walls has already been done. Anticoagulant drugs have been used to try to minimize secondary clotting and embolus formation, but have little or no effect on the progress of the disease. Vasodilator drugs are used to provide symptom relief, but are of no curative value.
Surgical treatment is available for certain high-risk situations. Balloon angioplasty can open up narrowed vessels and promote an unproved blood supply. The blood supply to the heart muscle can also be restored through a vein graft bypass. Large atheromatous and calcified arterial obstructions can be removed by endarterectomy, and entire segments of diseased peripheral vessels can be replaced by woven plastic tube grafts.
With regard to reduction of hypercholesterolemia, in some instances this can be achieved by modification of the diet and/or use of drugs thereby minimizing the risk of fatality of the disease. Reduction of serum cholesterol in humans has been achieved by consumption of dietary plant fiber and other effective components of foods. However, there remains a need for a safe and effective treatment for the above conditions which are often interrelated with minimal risk or side effects. As a preventive cure, diet plays a crucial role in bringing down the lipid parameters. In addition to diet and exercise, there is a need for a supplemental therapy, possibly to prevent these conditions and insure better health, particularly in people who are genetically predisposed to such conditions. The present invention fulfills these and other needs.
It has now been surprisingly found that stabilized rice bran derivatives reduce serum total cholesterol, LDL cholesterol, apolipoprotein B and triglyceride levels in mammals. As such, the present invention provides a method for reducing mammalian serum total cholesterol, LDL cholesterol, apolipoprotein B and triglyceride levels, by ingesting a stabilized rice bran derivative such as, enzyme treated stabilized rice bran, an insolubilized fraction and mixtures thereof, thereby reducing serum total cholesterol, LDL cholesterol, apolipoprotein B and triglyceride levels. In one embodiment, the derivative is administered in an amount of about 10 grams to about 100 grams per day total in at least 2 doses.
In another aspect, the present invention provides a method for increasing the HDL/LDL cholesterol ratio in mammalian serum, by ingesting a stabilized rice bran derivative such as, an enzyme treated stabilized rice bran derivative, an insolubilized fraction and mixtures thereof, thereby increasing the HDL/LDL ratio.
In still yet another aspect, the present invention provides a process for making an enzyme treated stabilized rice bran derivative by mixing stabilized rice bran with an aqueous solution to form about a 15% to about a 35% aqueous rice bran slurry; adding an enzyme to the aqueous rice bran slurry to convert starch to dextrin, thereby forming an enzyme treated slurry, and then drying the enzyme treated slurry to form an enzyme treated stabilized rice bran derivative.
I. Glossary
As used herein the term xe2x80x9capolipoprotein Bxe2x80x9d or xe2x80x9capoprotein Bxe2x80x9d or xe2x80x9cApo Bxe2x80x9d refers to the protein component of the LDL cholesterol transport proteins. Cholesterol synthesized de novo is transported from the liver and intestine to peripheral tissues in the form of lipoproteins. Most of the apolipoprotein B is secreted into the circulatory system as VLDL.
As used herein the term xe2x80x9carteriosclerosisxe2x80x9d is a degeneration of the walls of the arteries due to the formation of foam cells and aortic streaks which narrow the arteries. This limits blood circulation and predisposes an individual to thrombosis.
As used herein the term xe2x80x9catherosclerosisxe2x80x9d is a disease of the arteries in which fatty plaques develop on the inner walls, with eventual obstruction of blood flow.
As used herein the term xe2x80x9ccardiovascular diseasexe2x80x9d is a disease of the blood vessels of the circulation system caused by abnormally high concentrations of lipids in the vessels.
As used herein the term xe2x80x9cenzyme treated stabilized rice bran derivativexe2x80x9d refers to an enzyme treated stabilized rice bran made by mixing a stabilized rice bran with an aqueous solution in a 15% to about a 35% aqueous slurry w/w; adding an enzyme to the aqueous rice bran slurry to convert starch to dextrin; and then directly drying the dextrin solution to form an enzyme treated stabilized rice bran derivative. The enzyme treated stabilized rice bran comprises about 20% to about 30% total dietary fiber.
As used herein the term xe2x80x9cGRASxe2x80x9d means generally regarded as safe with respect to food additives.
As used herein the term xe2x80x9chypercholesterolemiaxe2x80x9d is a condition with elevated levels of circulating total cholesterol, LDL-cholesterol and VLDL-cholesterol as per the guidelines of the Expert Panel Report of the National Cholesterol Educational Program (NCEP) of Detection, Evaluation of Treatment of high cholesterol in adults (see, Arch. Int. Med. (1988) 148, 36-39).
As used herein the term xe2x80x9chyperlipidemiaxe2x80x9d or xe2x80x9chyperlipemiaxe2x80x9d is a condition where the blood lipid parameters are elevated in the blood. This condition manifests an abnormally high concentration of fats. The lipids fractions in the circulating blood are, total cholesterol, low density lipoproteins, very low density lipoproteins and triglycerides.
As used herein the term xe2x80x9clipoproteinxe2x80x9d such as VLDL, LDL and HDL, refers to a group of proteins found in the serum, plasma and lymph and are important for lipid transport. The chemical composition of each lipoprotein differs in that the HDL has a higher proportion of protein versus lipid, whereas the VLDL has a lower proportion of protein versus lipid.
As used herein the term xe2x80x9cstabilized rice bran derivative insolubilized fractionxe2x80x9d refers to a fraction of stabilized rice bran during a partitioning process. Specifically, after the stabilized rice bran aqueous slurry is enzymatically treated as discussed fully below, it is then pumped into a centrifuge where the insoluble fraction precipitates out of the aqueous solution. The insoluble fraction is collected and then dried, and subsequently ground into a powder. This powder is the insoluble portion. In a preferred embodiment, the constituent parts and their percentages are listed in Tables I and IV.
As used herein the term xe2x80x9cstabilized rice bran derivative solubilized fractionxe2x80x9d refers to a fraction during a partitioning process. Specifically, after the stabilized rice bran aqueous slurry is enzymatically treated, it is then pumped into a centrifuge where the insoluble fraction precipitates out of the aqueous solution. The aqueous material is pumped to a dryer and then dried. This dried aqueous portion produces the soluble fraction. In a preferred embodiment, the constituent parts and their percentages are listed in Tables I and V.
As used herein the term xe2x80x9ctriglyceridexe2x80x9d means a lipid or neutral fat consisting of glycerol combined with three fatty acid molecules.
As used herein the term xe2x80x9cxanthomatosisxe2x80x9d is a disease evidence by a yellowish swelling or plaques in the skin resulting from deposits of fat. The presence of xanthomas are usually accompanied by raised blood cholesterol levels.
II. Detailed Description
In harvested rice, also known as rough rice, the kernel is completely enveloped by the rice hull. The milling process removes the hull, which yields brown rice. The outer brown layer is then removed by an abrasive milling process to generate white rice. The separated brown layer is designated rice bran.
Rice bran is the mesocarp, i.e., the portion between the hull and rice grain, obtained by milling or polishing brown rice. It constitutes about 10% of rough rice. It is generally used as an animal feed. It contains about 18-24% fat, about 25% dietary fiber, about 14% protein and about 45% total carbohydrates besides several potent micronutrients. It is rich in B-complex vitamins, vitamin E and its isomers, minerals like potassium, magnesium, and phosphorous besides several potent antioxidants.
Stabilized rice bran can be commercially purchased or prepared using various methods. Most stabilization methods of rice bran result in inactivation of the lipases which are present, inactivation of the peroxidases, and inactivation of the microorganisms, while still maintaining the high levels of antioxidants in the rice bran. For a general discussion of stabilization and processing see, Rice Science and Technology, edited by W. E. Marshall and James I Wadswoth, (1994) pages 390-404.
Under normal conditions when brown rice is milled to rice, the oil in the bran and the lipases also in the bran come into mutual contact, resulting in rapid degradation of the rice oil to free fatty acids and glycerol. The rice bran becomes unpalatable and is no longer suitable for foodstuffs. However, if the lipases are inactivated, the rice bran is thereby stabilized and the adverse effects on the bran are avoided.
There are many suitable means to stabilize or inactivate the lipase in rice bran, however most commercial systems utilize moisture-added or dry extrusion methods. These systems are selected because of their relatively low energy requirements, low capital costs and ease of operation. Stabilization by dry extrusion utilizes shear, friction, and pressure to generate the heat required to inactivate the lipase. The temperature of the bran must reach a temperature of a minimum of 130xc2x0-140xc2x0 C. for up to 3 seconds to assure inactivation of the lipase.
Acceptable extrusion stabilization can be achieved under less harsh conditions by adding water or steam. The lipase is more heat sensitive at higher moisture and can therefore be inactivated at somewhat lower extrusion temperatures.
Residual peroxidase activity is generally used as the standard measure to make sure that lipase activity has been deactivated in stabilized rice bran. Peroxidase is generally considered to be more heat stable than lipase, and peroxidase activity assays are easier and more reliable than the assays for lipase. The process conditions required to inactivate peroxidase as well as lipase can also cause modification to or loss of antioxidants in the bran. This can lead to fewer fatty acids, but the bran can be subject to oxidative rancidity. In addition, because the rice bran is susceptible to mold, yeast and bacteria, the stabilization process must effectively reduce the microbiological load of the bran.
In addition to moisture added and extrusion techniques for stabilization, freezing and refrigeration of the rice bran result in economically viable processes to stabilize rice bran. Preferably, processes used to stabilize rice bran minimize the free fatty acid content, while maintaining high levels of antioxidants. Food grade stabilized rice bran is typically finely granulated, light tan in color and possesses a relatively bland flavor with a nutty, toasted overtones.
Stabilized rice bran is available commercially from Producers Rice Mill Inc. (Stuttgart, Ark.), Riceland Foods (Stuttgart, Ark.) Riviana Foods, Inc. (Houston, Tex.), Uncle Ben""s Inc. (Houston, Tex.) and TheRiceX Company (El Dorado Hills, Calif.). Due to different stabilization processes, stabilized rice bran will differ in composition and stabilization characteristics when derived from different manufacturers.
In order to generate the rice bran derivatives for use in the present invention, the rice bran is first stabilized, and then it is further separated into at least two fractions. These include, but are not limited to, a stabilized rice bran soluble derivative and a stabilized rice bran insoluble derivative. Preferably, the separation into the rice bran derivatives includes a nonchemical process i.e., an enzymatic process. In this process, partitioning or fractionation preferably proceeds as outlined hereinafter.
The stabilized rice bran is made into about a 15% to about 35% slurry, preferably, a 20-25 % slurry with potable water. An enzyme, which can include, but is not limited to, a dextranase, a maltase, a xcex1-amylase, and various other carbohydrate cleaving enzymes, is added to the batch converting the starch to dextrins. The slurry is heated to about 150xc2x0 F. to about 200xc2x0 F. using for instance, a steam injection cooker, a heat exchanger or other heating method. The slurry is then pumped to a horizontal centrifuge wherein the insoluble fraction is separated. The insoluble fraction is collected and then dried on a belt dryer, and subsequently ground into a powder. This powder is the stabilized rice bran insoluble fraction. The aqueous material is pumped to a drum dryer and then dried. This dried aqueous portion produces the stabilized rice bran solubilized fraction.
The enzyme treated stabilized rice bran can be generated using the rice bran slurry as described above. As such, in another aspect, the present invention relates to the process for making an enzyme treated stabilized rice bran derivative, comprising: admixing stabilized rice bran with an aqueous solution to form about a 15 % to about a 35% aqueous rice bran slurry, preferably a 20% to about a 30% aqueous rice bran slurry w/w; adding an enzyme to the aqueous rice bran slurry to convert starch to dextrin, thereby forming an enzyme treated slurry and then directly drying the enzyme treated slurry to form an enzyme treated stabilized rice bran derivative.
In a preferred embodiment of the foregoing process, after the enzyme is added to the slurry, the slurry is heated to about 100xc2x0 F. to about 200xc2x0 F. Preferably, the slurry is heated to about 150xc2x0 F. to about 200xc2x0 F. The slurry is then dried, wherein the drying is accomplished by a process such as belt drying, spray drying, drum drying and air drying. The drum drying process is preferred.
These stabilized rice bran derivatives are also available commercially from The RiceX Company of California. For the purpose of the invention, stabilized rice bran is available as RiceX(trademark) Stabilized Rice Bran. The insoluble derivative is available as RiceX(trademark) Fiber Complex and the soluble derivative is available as RiceX Ricelin(trademark) from The RiceX Company, El Dorado Hills, Calif.
The stabilized rice bran derivatives can take a variety of forms. They can be a powder, a food, a food supplement, a medical food, a liquid, a beverage, an emulsion or mixture thereof. In addition, they can be incorporated into other edible materials. To incorporate the rice bran derivative into the diet of a mammal various options include, but are not limited to, simply sprinkling the derivative on another food substance (i.e., salad, bread, cereal, etc.) being a major ingredient in a multigrain ready to eat cereal, incorporating it into a baked product (breads, muffins, waffles, etc), pasta, healthy dessert and snacks (athletic bar, healthy drink, etc.) and high fiber foods.
Stabilized rice bran contains about 18-23% fat, about 23-35% dietary fiber, about 12-16% protein, about 8-36% total carbohydrate and many potent microcomponents. Rice bran solubles contains about 15-40% fat, preferably 23-30% fat; about 0% to 25% dietary fiber, preferably about 0-20% dietary fiber; about 0% to 15% protein, preferably 6-9% protein and 25% to about 80% carbohydrates, preferably about 27-66% simple carbohydrate and is a water soluble fraction. Stabilized rice bran insoluble derivative contains about 5 %-20% fat, preferably 11-16% fat; about 40-65% dietary fiber, preferably 40-60% dietary fiber, and about 10-30% protein, preferably 18-22% protein (see, Table I).
With reference to Tables IV, V, VI and VII in Example 4, these derivatives have been shown to have at least seventy-five (75) potent anti-oxidants. The major antioxidant vitamin E and its isomers known as tocopherols (T) and tocotrienols (T3) are collectively called tocols. A tocol rich substance is a mixture containing one or more compounds selected from tocopherols (T), tocotrienols (T3), and tocotrienol-like (T3-like) compounds.
Antioxidant in stabilized rice bran derivatives include, but are not limited to, xcex3-oryzanol, xcex2-carotene, several known flavanoids, phytosterols, lipoic acid, and ferulic acid. Some of these compounds are present in high concentration, much more than in any of the known natural sources. It is believed that antioxidants particularly tocols, play a crucial role in significantly correcting certain metabolic disorders singularly or synergistically as discussed below.
The stabilized rice bran soluble derivative is a powdered emulsion of soluble stabilized rice bran and germ, and is easily digested and absorbed by the body. It can be taken by itself with a small amount of water to dissolve it in the mouth. It can also be mixed into liquids such as juice or hot drinks. Additionally, it is appropriate for use in baked goods and other foodstuffs as discussed above. There are a significant number of nutrients which have been discovered in rice bran solubles (stabilized rice bran solubilized derivatives).
The stabilized rice bran insoluble derivative binds bile acids thereby lowering serum cholesterol levels, decreases triglyceride levels thereby helping in the metabolism of cholesterol. It contains many highly potent antioxidants such as xcex2-carotene, xcex1, xcex2, xcex3, and xcex4 tocopherols and tocotrienols, phytate, oryzanols, glycosides and numerous phytosterols and polyphenols. The rice bran insoluble derivative can also be mixed into liquids such as juice or hot drinks. Additionally, it is appropriate for use in baked goods and other foodstuffs as discussed above.
The enzyme treated stabilized rice bran derivative can also be mixed into liquids such as juice or hot drinks. Additionally, it is appropriate for use in baked goods and other foodstuffs as discussed above.
The present invention is based on the discovery that persons suffering from hypercholesterolemia, hyperlipidemia, and atherosclerosis who ingest rice bran derivatives, such as the enzyme treated stabilized rice bran derivative, and stabilized rice bran insoluble derivative have significantly reduced serum total cholesterol, LDL cholesterol levels, apolipoprotein B and triglycerides. As such, the present invention relates to a method for reducing mammalian serum total cholesterol, LDL cholesterol, apolipoprotein B and triglyceride levels, the method comprises ingesting a stabilized rice bran derivative selected from the group consisting of an enzyme treated stabilized rice bran, an insolubilized fraction and mixtures thereof, thereby reducing serum total cholesterol, LDL cholesterol, apolipoprotein B and triglyceride levels in mammals. In a preferred embodiment, the mammal is a human individual.
It is presently preferred to administer the rice bran derivatives orally. In a preferred embodiment, the mammal ingesting the stabilized rice bran derivative is suffering from any number of diseases, including but not limited to, hyperlipidemia, cardiovascular disease, atherosclerosis, arteriosclerosis and xanthomatosis.
The stabilized rice bran derivative is ingested in an amount of about 10 grams to about 100 grams per day total, preferably in at least 2 doses. Preferably, the stabilized rice bran derivative is ingested in an amount of about 10 grams to about 40 grams per day total, and more preferably, in an amount of about 15 grams to about 30 grams per day total. The optimum dosage would be determined by the physician taking into account the age, weight and general health of the subject. The daily dosage can also be administered in one or several treatments over a period of time, such as by way of single or multiple doses per day or from sustained release compositions.
In another embodiment, the present invention relates to a method for increasing the HDL/LDL cholesterol ratio in mammalian serum comprising: ingesting a stabilized rice bran derivative selected from the group consisting of an enzyme treated stabilized rice bran derivative, an insolubilized fraction and mixtures thereof, thereby increasing said HDL/LDL cholesterol ratio in the mammal.
Elevated levels of LDL and VLDL are positively associated with coronary arteriosclerosis while the high levels of high density lipoproteins (HDL) are negative risk factors. Any dietary change which can decrease total cholesterol, LDL cholesterol levels will reduce risk of cardiovascular disease, atherosclerosis, arteriosclerosis and xanthomatosis. Thus, in this aspect, ingesting a stabilized rice derivative in an amount of about 10 grams to about 100 grams per day total, preferably in at least 2 doses will reduce the HDL/LDL ratio.
The stabilized rice bran derivative can be ingested alone or, more usually, in the form of a foodstuff comprising a therapeutically effective amount of the stabilized rice bran derivative in combination with an inert GRAS food component and an acceptable diluent or carrier therefor.
The stabilized rice bran derivative can also be used in association with other therapeutic agents including, for example, antibiotics or antiviral agents.
The potent antioxidants in stabilized rice bran derivatives, namely Vitamin E and its isomers, in combination with the other antioxidants present in it, play a major role in treating atherosclerosis by reducing the cholesterol levels, lipid levels, preventing platelet aggregation, preventing LDL-oxidation and restoring good blood supply to the heart.
The major antioxidants T and T3 are thought to inhibit a key enzyme, HMG CoA reductase, in liver microsomes involved in the biosynthetic pathway of cholesterol. The mechanism of T3, in inhibiting HMG CoA reductase involve post-transcriptional suppression of HMG CoA reductase in a manner mimicking the action of putative non-sterols feedback inhibitors.
Without being bound to a particular theory, it is believed that the bioactive components in rice bran derivatives, and their associated mechanisms, positively effect the management of atherosclerosis, cardiovascular disease and the associated conditions of hypercholesterolemia and hyperlipidemia. These bioactives seem to act synergistically, creating an enhanced effect not expected when one evaluates the individual compounds present in rice bran derivatives. The major bioactive components present in the rice bran derivatives are tocopherols, tocotrienols, xcex3-oryzanol, phytosterols, polyphenols, inositol, B vitamins, protein, fiber, and fat (see, Tables IV-VII). Some of the biological effects of these components and the mechanisms involved are set forth below.
1. Enzyme inhibitions: three enzymes, namely HMGCoA reductase, ACAT transferase and esterase are inhibited. HMGCoA reductase, a key enzyme involved in the cholesterol biosynthesis is inhibited by the tocotrienols, post transcriptionally, reducing the synthesis of cholesterol resulting in low circulating cholesterol.
Acyl coenzyme A transferase (ACAT), inhibition is brought about by xcex3-oryzanol leading to:
a) the prevention of cellular cholesterol esterification thereby enriching high density lipoprotein cholesterol (HDL) with free cholesterol;
b) elevation of HDL, a positive effect, and decreased synthesis of very low density lipoprotein cholesterol (VLDL); and
c) increased clearance of cholesterol as bile acids and bile salts.
The net result is lower circulating cholesterol. Cholesterol esterases are inhibited by cycloartenol, a component of xcex3-oryzanol, resulting in a slower hydrolysis of cholesterol esters and decreased absorption. This results in lower circulating total cholesterol.
2. xcex3-Oryzanol inhibits platelet aggregation, and aortic streaks thus reducing atherosclerosis.
3. Rice bran derivatives contain a significant variety and concentration of antioxidants. Antioxidants such as tocopherols, tocotrienols, xcex3-oryzanol, polyphenols as ferulic acid, and lipoic acid are involved in the repair of free radical damage, preventing low density lipoprotein cholesterol (LDL) oxidation, resulting in the reduction of vascular damage that can lead to cardiovascular disease.
4. Cycloartenol, a component of xcex3-oryzanol, has a structure similar to cholesterol and competes with receptor sites of cholesterol. This causes a sequestration of cholesterol as bile salts and bile pigments, thus maintaining lower levels of circulating cholesterol.
5. Phytosterols and fiber facilitate cholesterol sequestration from the body through increased excretion of bile salts and bile acids, resulting in lower levels of circulating cholesterol. The effect of soluble fiber in cholesterol management is well documented in the literature.
6. The protein, fat (with high levels of polyunsaturated and monounsaturated fatty acids), and B vitamins also contribute to the hypocholesterolemic effect.